NDLI: Inhaled insulin-intrapulmonary, intranasal, and other routes of administration: mechanisms of action.

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Inhaled insulin-intrapulmonary, intranasal, and other routes of administration: mechanisms of action.

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Inhaled insulin-intrapulmonary, intranasal, and other routes of administration: mechanisms of action.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Henkin, R. I.
Description	Country affiliation: United States Author Affiliation: Henkin RI ( Center for Molecular Nutrition and Sensory Disorders, The Taste and Smell Clinic, Washington, DC, USA. rihenkin@earthlink.net)
Abstract	BACKGROUND: After discovery of insulin as a hypoglycemic agent in 1921 various routes of administration to control blood glucose were attempted. These included subcutaneous, oral, rectal, sublingual, buccal, transdermal, vaginal, intramuscular, intrapulmonary and intranasal delivery systems. While each delivery system controlled hyperglycemia the subcutaneous route was given priority until 2006 when the Federal Drug Administration (FDA) approved the first commercially available pulmonary inhaled insulin. METHODS: A review of major publications dealing with intrapulmonary administration of insulin was made to understand the physiological basis for its use, its efficacy in controlling hyperglycemia, its side effects and a comparison of its efficacy with other delivery methods. RESULTS: The large surface area of the lung, its good vascularization, capacity for solute exchange and ultra thin membranes of alveolar epithelia are unique features that facilitate pulmonary insulin delivery. Large lung surface area ( approximately 75 m(2)) and thin alveolar epithelium ( approximately 0.1-0.5 microm) permit rapid drug absorption. First pass metabolism avoids gastrointestinal tract metabolism. Lung drug delivery depends upon a complex of factors including size, shape, density, charge and pH of delivery entity, velocity of entry, quality of aerosol deposition, character of alveoli, binding characteristics of aerosol on the alveolar surface, quality of alveolar capillary bed and its subsequent vascular tree. Many studies were performed to optimize each of these factors using several delivery systems to enhance pulmonary absorption. Availability was about 80% of subcutaneous administration with peak activity within 40-60 min of administration. Intranasal insulin delivery faces a smaller surface area ( approximately 180 cm(2)) with quite different absorption characteristics in nasal epithelium and its associated vasculature. Absorption depends upon many factors including composition and character of nasal mucus. Absorption of intranasal insulin resulted in a faster absorption time course than with subcutaneous insulin. INTERPRETATION: After many studies the FDA approved Pfizer's product, Exubera, for intrapulmonary insulin delivery. While the system was effective its expense and putative side effects caused the drug company to withdraw the drug from the marketplace. Attempts by other pharmaceutical companies to use intrapulmonary insulin delivery are presently being made as well as some minor attempts to use intranasal delivery systems.
File Format	HTM / HTML
ISSN	08999007
Issue Number	1
Volume Number	26
e-ISSN	18731244
Journal	Nutrition
Language	English
Publisher	Elsevier
Publisher Date	2010-01-01
Publisher Place	United States
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Discipline Nutritional Sciences Hypoglycemic Agents Administration & Dosage Insulin Lung Metabolism Nasal Mucosa Absorption Administration, Inhalation Administration, Intranasal Aerosols Chemistry Drug Administration Routes Humans Time Factors Journal Article Review
Content Type	Text
Resource Type	Article
Subject	Nutrition and Dietetics Endocrinology, Diabetes and Metabolism

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